Effects of a 12-week aerobic exercise programme on human immunodeficiency virus-associated neurocognitive disorder in Nigeria

Abstract

BACKGROUND: The burden of the human immune deficiency virus (HIV)-associated neurocognitive disorder (HAND) continued to expand despite widespread use of antiretroviral therapy (ART). Being diagnosed with HAND impacts medication adherence, activities of daily living and quality of life, and increases risk behaviours among people living with HIV (PLWHIV). This consequently disrupts efforts to contain HIV transmission and maintain a quality life for PLWHIV. Several efforts have been made to eradicate HAND, with early intensification with ART being the most remarkable. The increase in the incidence of mild but limiting forms of HAND amongst PLWHIV adherent to ART coupled to the risk of polypharmacy and organ damage and its associated burden of ART warrants the development of behavioural adjuvants. This thesis sought to unravel the current epidemiological and diagnostic situations of HAND, explored the putative rehabilitative options in an attempt to provide a therapeutic adjunct for HAND particularly in sub-Saharan Africa which bears the brunt of the HAND burden.

AIM: The overarching aim of this PhD thesis is to further the development of rehabilitative interventions adjunct to ART for effective rehabilitation of individuals with HAND. We explored the position of evidence regarding the burden of HAND in sub-Saharan Africa, examined the functional consequences in the combined ART era, mapped out the putative rehabilitative options, further explored the therapeutic potential of physical activity interventions and thereafter examined the efficacy of aerobic exercise for HAND.

METHODS: Extensive literature reviews were conducted using evidence synthesis skills and methods. In phase one, we undertook a scoping review to map out rehabilitative interventions for HAND, a pilot study to examine psychometric properties of our study instruments, a normative study to produce reference scores for selected NP battery tests, and a cross-sectional study to determine the prevalence of HAND. In phase 2, a randomised controlled trial was conducted to ascertain the effects of a 12-week aerobic exercise programme on HAND severity, quality of life and activity and participation level.

RESULTS: In south-eastern Nigeria, the prevalence of HAND was 59.1%, with asymptomatic neurocognitive impairment ranking as the highest (44.9%), followed by mild neurocognitive disorder (12.3%), and HIV-associated dementia (1.9%). Factors associated with HAND were education (χ2 = 16.492, p = .011), duration of HIV infection (χ2 = 3.645, p = .013) and cognitive complaints (χ2 = 108.87, p < .001). We identified two putative rehabilitative intervention options for HAND namely psycho-cognitive training, and physical activity interventions. Psycho-cognitive training is an effective option for HAND, although the conditions of far-transfer effects are yet to be set forth. Observational studies showed that engagement in physical activity reduced the odds of decline in neurocognition in PLWHIV. However, our meta-analysis revealed that physical activity was not superior to control over cognitive functioning in individuals undiagnosed with HAND (Z = 0.86; p = 0.39; and I2 = 94%). The lack of efficacy may be attributed to the use of a mixed population, short-term and low-intense exercise prescriptions. In view of this, our trial was designed to overcome the identified gaps. Our RCT data demonstrated that aerobic exercise produced a five-fold reduction in working memory impairment (OR= 5.14; CI=2.6-10.4; NNT=6), and an approximately two-fold reduction in the subjective cognitive complaint (OR=2.11; CI=1.4-3.3, NNT= 5). Reduction in attention impairment (OR=1.55, 95 CI=1.0-2.4; NNT=5) and HAND prevalence (OR=1.8, 95 CI=1.2-2.8); NNT=8) were observed three months post-intervention. Also, the exercise group showed a greater improvement in overall quality of life (p = 0.001) and activity and participation level (p <0.001) compared to the control group. Viral load (p = 0.049) and depressive symptoms (p = 0.039) were lower in the exercise group compared to the control group.

CONCLUSIONS: The burden of HAND in South-eastern Nigeria is high. Low education, cognitive complaints and HIV chronicity are some of the factors associated with HAND. The lack of variety in the normative score for the DST and the motor skill component of the international HIV dementia scale moving from mild to severe impairment limit their utility in our setting. Psycho-cognitive training and physical activity intervention are the putative rehabilitative options for HAND. Among PLWHIV with HAND, the neuroprotective effects of aerobic exercise appear to be selective and vary depending on the cognitive abilities impaired. Individuals with working memory and attention deficits may benefit more from moderate-intensity aerobic exercise. Exercise effect on neurocognition may be evolutionary, with optimum effect occurring during periods of inactivity following exercise. Aerobic exercise provides a short-term improvement in quality of life and activity and participation level amongst individuals with HAND. The parameters and conditions for optimum exercise efficacy for HAND requires further studies.